Fibroids are benign uterine tumors that have been estimated to occur to some degree in more than 75% of women of reproductive age (Cancer Research 62:3766-3772 (2002); Cramer, et al., Am. J. Clin. Pathol. 94:435-438 (1990)). About 20-50% of women with fibroids experience symptoms and, depending upon the size and location of their tumors, these may include infertility, urinary incontinence, constipation, menorrhagia (prolonged and profuse uterine bleeding) and abdominal pain (Vollenhoven et al. Brit. J Obstet. Gynaecol. 97:285-298 (1990)). More than 200,000 of these women undergo hysterectomies each year in the United States (Walker, et al., Science 308:1589-1592 (2005)).
Although the causes of fibroids are not completely understood, genetic factors appear to be an important contributing component. In this regard, recurring cytogenetic abnormalities associated with human leiomyoma have been mapped to two specific high mobility group (HMG) gene loci. Rearrangements at 12q14-15 map to HMGA2, formerly HMGIC, and rearrangements at 6p21 map to HMGA1, formerly HMGI/Y (Hess, et al., Am. J. Clin. Pathol. 109:251-261 (1998); Ligon, et al., Genes Chromosomes Cancer 28:235-245, (2000)). Alterations involving at least one of these loci have been observed in up to 30% of chromosomally abnormal leiomyomas.
The genetic rearrangements described above are somatic in nature, i.e., they occur in tumor cells and would not ordinarily be expected to be present in the normal cells of a patient or transmitted to a patient's offspring. Whether there are hereditary factors that predispose women to develop these rearrangements or uterine fibroids in general is largely unknown. The identification of such factors could help in counseling women concerning reproductive issues and in deciding between therapeutic options.